Intravascular device with netting system

ABSTRACT

An intravascular device for keeping open a previously constricted site within a vessel and for minimizing tissue debris at such a site from closing off the vessel is provided. The device includes an expandable substantially tubular body defined by a framework having a plurality of openings. The device also includes a flexible netting system having a structural design for extending across each of the openings. Such a design allows the netting system to expand along with each opening in the framework to minimize release of tissues debris at the site from closing the lumen of the vessel. The netting system can include a plurality of pores to permit communication between fluid flow within the vessel and the vessel wall, and at least one pharmacotherapeutic agent for the treatment or prevention of certain conditions. A method for placing the device at a site of interest is also provided.

FIELD OF THE INVENTION

The present invention relates to intravascular devices, and moreparticularly, to stents for maintaining an open lumen within a vesseland for minimizing thrombus formation as well as release of tissuedebris therefrom to prevent blockage of fluid flow within the vessel.

RELATED ART

Many medical intravascular devices are currently being used eithertemporarily or permanently inside the human body to address conditionsassociated with high blood pressure, diabetes, and stroke. One exampleof an intravascular device is a stent for use in, for instance, coronaryangioplasty. Stents are small mechanical devices that can be implantedwithin a vascular structure, such as a blood vessel or an artery, andcan be mechanically expanded to maintain an open lumen at a constrictedlocation to permit a substantially clear flow path therethrough. A stentcan also act to support a vessel wall in areas vulnerable to collapse.

The mechanical reopening of a constricted vessel can sometimes lead toinjuries of the tissues at the site of constriction or closure. Suchinjuries can often stimulate thrombus formation at such a site, as wellas release of tissue debris that may subsequently act to block fluidflow within the vessel. Moreover, if permitted to proliferate,pronounced neointimal hyperplasia or restenosis can result. Thrombusproduction remains one of the most common post-stenting clinicalproblem, and requires effective intervention or counter-measures toprevent and/or control its reoccurrence.

Currently, methods for preventing or controlling thrombus arespecifically aimed at influencing factors believed to be involved in thebody's response to external or internal tissue stimulants, such asangioplasty, stenting procedures, and/or viruses. Common countermeasureswhich have been used to prevent or control restenosis generally fallinto the one of several categories, including (1) mechanicalatheroablative techniques, such as debulking, vascular filters, andemboli-trapping devices, (2) ultrasound-initiated atheroablativetechniques, (3) light-assisted procedures, predominantly excimer laserangioplasty, (4) pharmacological agents and gene therapy, (5)ultraviolet photophoresis, believed to be an immune modulator, (6)radiation therapy, such as external and endovascular brachytherapy, and(7) re-stenting.

In addition, modifications to stent designs and materials have beenproposed to prevent and/or control restenosis. In one approach,non-metallic, biodegradable stent materials, such as high molecularweight Poly-1-lactic acid (PLLA) is used.

Numerous inorganic coatings and surface treatments have also beendeveloped to improve chemical inertness and biocompatibility of metallicstents. Some coatings, such as gold, however, yield a higher rate ofin-stent restenosis than uncoated stents. Others, including siliconcarbide and turbostatic carbon, show promise but additional studies mustbe done.

Organic coatings, including both synthetic and natural coatings, havealso been widely studied. Among the synthetic coatings studied areDacron, polyester, polyurethane, polytetrafluoroethylene (PTFE),polyethylacrylate/polymethylmethacrylate, polyvinyl chloride, silicone,collagen, and iridium oxide. Results of studies, such as those withPTFE-coated stents, are disappointing or mixed at best, as there arehigh occurrences of late thrombo-occlusive events. With only a very fewexceptions, the general consensus is that any favorable outcome was notassociated with treatment of conventional in-stent restenosis usingPTFE-coated stents.

Intracoronary intervention have also been employed to reduce neointimaformation by reducing smooth muscle cell proliferation after balloonangioplasty. However, such intervention is often complicated by subacuteand late thrombosis. Coronary thrombo-aspdrugiration and coronarypulsed-spray procedures, followed by immediate endovascular therapy,have also been particularly helpful in removing thrombotic materialassociated with plaque.

In addition, pharmacotherapeutic agents have been used for the treatmentof some of the major post-angioplasty complications, includingimmunosuppresants, anticoagulants and anti-inflammatory compounds,chemotherapy agents, antibiotics, antiallergenic drugs, cell cycleinhibitors, gene therapy compounds, and ceramide therapy compounds.Pharmacotherapeutic agents can be delivered either systemically orlocally. Systemic treatment has shown limited success in reducingrestenosis following stent implantation, a result believed to be due toinadequate concentration of the pharmacotherapeutic agents at the siteof injury. Increased dose administration, however, is constrained bypossible systemic toxicity. It has been observed that local delivery ofhigher doses via drug eluting stents can significantly reduce adversesystemic effects. However, the local delivery of drugs via stents may belimited by the amount of surface area for drug elution.

Gene therapy have also been employed in the treatment of thrombusproduction. The procedure is directed towards smooth muscle cells andinvolves gene transfer via DNA, with or without integration ofchromosomes, into selected cells. In transduction without integration,the gene is delivered to both cytoplasm and nucleus and is thereforenon-selective. Gene transfer for integration employs retrovirus toaffect growth stimulators.

Antibiotics, likewise, has been used in the treatment of coronary arterydisease. It is known that antibiotics are effective in controllinginflammation caused by a variety of infectious agents found in fattyplaques blocking the arteries. Results of clinical investigation, suchas with azithromycin, suggest a modest antibiotic benefits for heartpatients.

Similarly, a phospholipid exhibiting immunosuppressive properties, hasbeen shown to block T-cell activation and proliferation, inhibitTaxol-induced cell cycle apoptosis, and activate protein kinase signaltranslation in malignant myogenic cells. Rapamycin and its analogsexhibit anti-tumor activities at relatively low dose levels, whileinducing only mild side effects, an extremely important aspect ofpatient care.

SUMMARY OF THE INVENTION

The present invention provides, in one embodiment, an intravasculardevice, such as a stent, for keeping open a previously constrictedintravascular site within a vessel and for minimizing tissue debris fromsuch a site from closing off the vessel. The device may also be used forlocal delivery of at least one pharmacotherapeutic agent to theintravascular site for the treatment or prevention of restenosis.

The intravascular device, in accordance with an embodiment of theinvention, includes an expandable substantially tubular body forplacement against a vessel wall. The body of the device, in anembodiment, can be defined by a framework having a plurality ofopenings. The device also includes a flexible netting system having astructural design for extending across each of the openings. Such adesign allows the netting system to expand along with each opening inthe framework to minimize occurrence of thrombus formation and tissuesdebris from closing the lumen of the vessel. The netting system caninclude a plurality of pores to permit communication between fluid flowwithin the vessel and the vessel wall, and at least onepharmacotherapeutic agent for the treatment or prevention of certainconditions. In one embodiment, the netting system includes a pluralityof extensible panels, each designed to be securely situated within anopening of the matrix. Alternatively, the netting system includes a meshdisposed on a substantially flexible matrix, such that the mesh can beplaced circumferentially about the framework of the body. If desired,the flexible matrix can be provided with sufficient strength to permitthe netting system to keep the lumen of the vessel temporarily openuntil the framework can be expanded. The device of the presentinvention, in an embodiment, can further include a second expandablesubstantially tubular framework concentrically positioned within thefirst framework of the tubular body.

The present invention also provides a method for the placement of anintravascular device within a vessel. The method includes initiallyproviding a device having an expandable substantially tubular bodydefined by a framework having a plurality of openings, and a pluralityof netting panels situated within each of the openings. Next, the devicemay be advanced along a lumen of the vessel to a site of interest.Thereafter, the framework may be expanded at the site of interest toallow the lumen of the vessel to remain open. The device maysubsequently act to elute at least one pharmacotherapeutic agent fortreatment of a condition from the netting panels. The netting panels mayalso act to retain tissue debris between the netting panels and a vesselwall.

The present invention further provides another method for placement ofan intravascular device within a vessel. The method includes providing adevice having an expandable substantially tubular body defined by aframework having a plurality of openings, and a mesh disposed on asubstantially flexible matrix loosely positioned circumferentially aboutthe framework. Next the device may be advanced along a lumen of thevessel to a site of interest. Thereafter, the framework may be expandedat the site of interest, and the mesh on the flexible matrix be allowedto be secured between the framework and a vessel wall. In oneembodiment, prior to expanding the framework, the flexible matrix onwhich the mesh is disposed may be expanded. The device may subsequentlyact to elute, from the mesh, at least one pharmacotherapeutic agent fortreatment of a condition. The mesh may also act to retain tissue debrisbetween the netting panels and a vessel wall.

In another embodiment, a further method for placement of anintravascular device within a vessel is provided. The method includesinitially providing a device having a first expandable, substantiallytubular framework having a plurality of openings, a plurality of nettingpanels situated within each of the openings, and a second expandablesubstantially tubular framework concentrically positioned within thefirst tubular framework. Next, the device may be advanced along a lumenof the vessel to a site of interest. Thereafter, the device may beexpanded at the site of interest to allow the lumen of the vessel toremain open. In one embodiment, the first and second tubular frameworkmay be expanded independently. Alternatively, the first and secondtubular framework may be expanded simultaneously. The device maysubsequently act to elute at least one pharmacotherapeutic agent fortreatment of a condition from the netting panels. The netting panels mayalso act to retain tissue debris between the netting panels and a vesselwall.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates a side view of an intravascular device in accordancewith one embodiment of the present invention.

FIGS. 2A-B illustrate a detailed view of a portion of the device in FIG.1 with a netting system in accordance with an embodiment of the presentinvention.

FIG. 3 illustrates a longitudinal section view of another intravasculardevice in accordance with one embodiment of the present invention.

FIG. 4 illustrates a perspective view of an intravascular device havingconcentric frameworks in accordance with another embodiment of thepresent invention.

DETAILED DESCRIPTION OF SPECIFIC EMBODIMENTS

As illustrated in FIG. 1, there is shown in accordance with anembodiment of the present invention, an expandable intravascular device,such as a stent, for keeping open a lumen of a previously constrictedintravascular site and for minimizing tissue debris from such a sitefrom closing off the lumen. The device, in an embodiment, may also beused for local delivery of at least one pharmacotherapeutic agent to theintravascular site for the treatment or prevention of restenosisresulting from thrombus formation.

The intravascular device 10, as illustrated in FIG. 1, includes asubstantially tubular body 11 for placement against a vessel wall andstructural support thereof. The body 11, in an embodiment, may bedefined by an expandable framework 12 having a plurality of openings 13.As the stent 10 is used to maintain an opening at a site which may havebeen previously constricted to provide a passage therethrough, theexpandable framework 12 of stent 10 needs to be made from abiocompatible material that is sufficiently strong to maintain andsupport the opening. In one embodiment of the invention, a material fromwhich the framework 12 may be made includes a metal, a metal alloy,plastic, or a combination thereof. By providing the stent 10 with, forinstance, a metallic framework 12, the stent 10 may also be visualized,for example, by flouroscopy during placement of the stent 10 within avessel. Of course, the framework 12 may be made from other strongmaterials, for instance, polymeric materials that are well known in theart.

The stent 10 may also include a flexible netting system 14 extendingacross each of the openings 13 on framework 12. Since the stent 10 maybe positioned at a previously constricted site, the presence of thenetting system 14 on framework 12 can act to minimize the occurrence oftissue debris at such a site from being released into the lumen of thevessel and possibly closing off the lumen. In particular, the nettingsystem 14 can act to retain tissue debris between it and the vesselwall. In one embodiment, as the flexible netting system 14 haselasticity, the netting system 14 may be allowed to radially extendthrough openings 13 and into the lumen of the vessel at from about 0.01mm to about 0.5 mm. Although extending into the lumen, the nettingsystem 14 may be designed so that such extension still permits about 75%to about 80% of the lumen to remain open for sufficient fluid flowthrough the vessel.

Still referring to FIG. 1, the netting system 14 may comprise aplurality of pores 141 to permit fluid communication between a vesselwall and fluid components within the vessel, such as blood. The pores141, in an embodiment, may be displaced throughout the netting system 14in similar or different patterns or shapes. For example, the nettingsystem 14 may comprise a series of linked chains 22, as shown in FIG.2A. In one embodiment, pores 141 may range from about 1/1000 to about1/10 the size of an opening 13 in framework 12. Preferably, pores 141may range from about 0.1 μm to about 100 μm. Regardless of the size, thepores 141 should act to permit fluid communication with the vessel wallwhile minimizing the occurrence of tissue debris from passingtherethrough. In addition, is believed that the presence of pores 141can provide proper tissue (e.g., endothial cell) growth at, for example,a post-angioplasty stented site. Furthermore, the pores 141 may providea space through which surrounding tissue may extend to secure the stent10 in place.

The netting system 14 may also serve as a storage and direct transportvehicle for the local delivery of, for instance, thrombus-inhibitingpharmaceuticals To that end, the netting system 14 may be provided witha substantially uniform thickness and may be made from a biocompatiblematerial, so as to minimize toxic reactions from surrounding tissues.The presence of the netting system 14 also provides additional surfacearea from which the pharmacotherapeutic agent can be eluted ordelivered.

Examples of pharmacotherapeutic agents which may be incorporated withinthe netting system 14 include Rapamycin, a phospholipid exhibitingimmunosuppressive properties. In addition, Heparin andglycosaminoglycans are anticoagulants which may be delivered locallyafter intravascular device implantation. These anticoagulants interactwith growth factors and other glycoproteins, which may reduce neointimalproliferation.

Abciximab is a genetically engineered fragment of a chimerichuman-murine mono-clonal antibody. It is a glycoprotein inhibitor andworks by inhibiting the binding of fibrinogen and other substances toglycoprotein receptor (GBIIb/IIIa) on blood platelets integral toaggregation and clotting. Abciximab appears to be effective inpreventing platelet aggregation when used with aspirin and heparin, andappears to be effective in preventing abrupt closure of arteries.

Antibiotics, likewise, can be used in the treatment of coronary arterydisease. It is known that antibiotics are effective in controllinginflammation caused by a variety of infectious agents found in fattyplaques blocking the arteries. Azithromycin has been observed to providemodest antibiotic benefits for heart patients.

Other pharmacotherapeutic agents which can be incorporated into thenetting system 14 includes radionuclides for use in the treatment ofdiseased tissues, and enzymes, which may be encapsulated within acarrier, for instance, a biodegradable sol-gel capsule dispersed withinthe netting system 14.

It should be appreciated that the concentration of pharmacotherapeuticagent or agents, as well as the rate of release can be adjustedaccording to the treatment for which the stent 10 is being used, so thatthe release rate of the agent or agents would be appropriate andsufficient for the treatment. For example, the netting system 14 may becoated with multiple layers, each having at least onepharmacotherapeutic agent dispersed therein.

Looking now at FIGS. 2A-B, the netting system 14 of the presentinvention may include a plurality of individual panels 21, each securelypositioned within an opening 13 of framework 12. Each of the panels 21,in an embodiment, can include a structural design that provides it withsufficient strength to permit retention of tissue debris between thepanel 21 and the vessel wall. In accordance with one embodiment, astructural design that can be implemented includes a series ofextensible chained links 22 made from, for example, a metal, metalalloy, a polymer or a combination thereof. Such a design also permitseach panel 21 to expand along with each opening 13 during expansion ofthe framework 12, as shown in FIG. 2B. Of course, other structuraldesigns may be employed, so long as they permit each panel 21 to besufficiently strong, expand accordingly, and retain tissue debris fromfalling into the lumen of the vessel.

Looking now at FIG. 3, there is illustrated a netting system 30 inaccordance with another embodiment of the present invention. Nettingsystem 30, as shown therein, may include a mesh 31, in a form of asheet, for example, disposed on a substantially flexible matrix 32. Byproviding the netting system 30 with a flexible design, the nettingsystem 30 may be placed circumferentially about the framework 12 ofstent 10. Although flexible in design, it should be noted that the mesh31 and matrix 32 structurally can provide the netting system 30 withsufficient strength to retain tissue debris between the netting system30 and vessel wall 33. In addition, the utilization of the flexiblematrix 32 can allow the mesh 31 thereon to expand along with theopenings 13 during expansion of the framework 12. The netting system 30,in one embodiment, may be loosely positioned circumferentially about theframework 12. As such, the netting system 30 may be pulled ontoframework 12 or pulled off framework 12 without damaging the nettingsystem 30. It should be appreciated that although loosely positionedabout the framework 12, subsequent to its expansion within a vessel, thenetting system 30 may be pushed against the vessel wall 33 by theframework 12 to minimize movement of the netting system 30 thereat.Alternatively, the netting system 30 may be loosely secured to varioussections of framework 12, for example, at multiple intersections 121between filaments 122. Nevertheless, similar to the non-securedembodiment, the netting system 30 may be pushed against the vessel wall33 by the framework 12 to remain secured thereat.

In accordance with another embodiment of the invention, the nettingsystem 30 may be provided with enhanced rigidity to permit temporarysupport of the vessel wall until framework 12 can be expanded. With sucha design, if necessary, the netting system 30 may be expanded at thesite of interest initially independently of the framework 12.Thereafter, the framework 12, concentrically positioned within thenetting system 30, may be expanded to provide the necessary support tothe vessel wall. To provide the netting system 30 with a structuraldesign sufficient to maintain the lumen of the vessel temporarily open,the flexible matrix 32 may be designed to include from about 50% toabout 70% by volume of the filaments defining the framework 12. Ofcourse, the amount of filaments making up the flexible matrix 32 can beless, so long as the matrix can temporarily keep the vessel wall fromclosing until the framework 12 can be expanded. In one embodiment, thestrength and structural property of the netting system 30 can becalculated or adjusted by choice of materials, the amount (i.e., volume)of materials, or a combination thereof.

As an alternate embodiment, the netting system 30 may be a stent itself.In particular, looking now at FIG. 4, the netting system can be an outerstent A concentrically positioned about framework 12 (i.e., inner stentB). Although not illustrated as such, the two stents in this embodimentmay be substantially similar to one another. The outer stent A ornetting system 30, in one embodiment, may include individual panels 41,like the panels 21 shown in FIG. 2A, securely positioned within theopenings of its framework. These panels 41, similar to panels 21, canact to retain tissue debris from falling into the lumen of the vessel,as well as to elute at least one of the pharmacotherapeutic agents notedabove to a site of interest in order to minimize the occurrence ofthrombus formation.

In use, intravascular device, such as stent 10 shown in FIG. 1, may beadvanced along a lumen of a vessel to a site of interest, for example, apreviously constricted site, an area where a cap may be thin, such asthat associated with a vulnerable plaque, or a calcification site, suchas that seen in carotid arteries. Thereafter, stent 10, and inparticular, its framework 12, may be expanded at the site of interest toengage and support a wall of the vessel.

In the embodiment where the netting system is similar to flexiblenetting system 30, the framework 12 may be expanded at the site ofinterest, so that the netting system 30 may be expanded along therewith.Once the framework 12 is fully expanded, the netting system 30 may besecured between the framework 12 and the vessel wall.

In an alternate embodiment, where the netting system 30 may besufficiently rigid, the netting system 30 may initially be expanded toengage the vessel wall to provide temporary support thereat.Subsequently, the framework 12, concentrically positioned within theexpanded netting system 30, may be expanded to secure the netting system30 between the vessel wall and the framework 12. A similar expansionprotocol can be implemented in an embodiment where the netting system 30may be a stent itself and a second stent exists concentricallytherewithin.

Once the stent 10 has been expanded, the netting system may be permittedto facilitate the elution of at least one pharmacotherapeutic agent tothe site of interest. In addition, the netting system may act to retaintissue debris between the netting system and a vessel wall.

The stent of the present invention may be used to support and maintainan opening within a variety of different vessels. For instance, thestent may be placed within a coronary artery or a carotid artery tofacilitate fluid flow through such arteries. By facilitating fluid flow,a heart attack or a stroke may be avoided in patients who may havecalcification or vulnerable plaques within their arteries as a result ofaging, high blood pressure, diabetes or other similar physicalconditions. The stent may also be used to constrict a passageway, forinstance, the coronary sinus, among others. To constriction apassageway, the stent may be made so that it is substantially resistantto expansion, so as to permit the tubular framework to constrict thetubular framework. The stent may also be used as a renal stent,gastrointestinal stent, radiation and chemotherapy stent.

While the invention has been described in connection with the specificembodiments thereof, it will be understood that it is capable of furthermodification. For instance, the stent may be adapted for use with otherintravascular devices for implantation within a patient's body.Furthermore, this application is intended to cover any variations, uses,or adaptations of the invention, including such departures from thepresent disclosure as come within known or customary practice in the artto which the invention pertains, and as fall within the scope of theappended claims.

What is claimed is:
 1. A method for placement of an intravascular devicewithin a vessel, the method comprising: providing a device having anexpandable substantially tubular body defined by a framework having aplurality of openings, and a plurality of individual netting panels eachsecurely positioned within each of the openings, such that the nettingpanels can expand along with each opening in the framework to retaintissue debris between the netting panels and a vessel wall, the nettingpanels having a structural design with sufficient strength to preventthe tissue debris from falling through the openings and into the vessel,wherein the netting panels are capable of extending radially into thetubular body defined by the framework while permitting about 75% toabout 80% of the lumen to remain open for sufficient fluid flow throughthe vessel; advancing the device along the lumen of the vessel to a siteof interest; and expanding the framework at the site of interest toallow the lumen of the vessel to remain open.
 2. A method as set forthin claim 1, wherein the step of providing includes supplying the nettingpanels with at least one pharmacotherapeutic agent.
 3. A method as setforth in claim 2, further including allowing the pharmacotherapeuticagent to be eluted from the netting panels to a vessel wall.
 4. A methodfor placement of an intravascular device within a vessel, the methodcomprising: providing a device having a first expandable substantiallytubular framework having a plurality of openings, a plurality ofindividual netting panels each securely positioned within each of theopenings to retain tissue debris between the netting panels and a vesselwall, the netting panels having a structural design with sufficientstrength to prevent the tissue debris from falling through the openingsand into the vessel, wherein the netting panels are capable of extendingradially into the tubular body defined by the framework while permittingabout 75% to about 80% of the lumen to remain open for sufficient fluidflow through the vessel, and a second expandable substantially tubularframework concentrically positioned within the first tubular framework;advancing the device along the lumen of the vessel to a site ofinterest; and expanding the device at the site of interest to allow thelumen of the vessel to remain open.
 5. A method as set forth in claim 4,wherein the step of providing includes supplying the netting panels withat least one pharmacotherapeutic agent.
 6. A method as set forth inclaim 5, further including permitting the pharmacotherapeutic agent tobe eluted from the netting panels to a vessel wall.
 7. A method as setforth in claim 4, wherein the step of expanding includes expanding thefirst tubular framework and the second tubular framework independently.8. A method as set forth in claim 4, wherein the step of expandingincludes expanding the first tubular framework and the second tubularframework simultaneously.